Cyclic and acyclic organophosphorus agents will be designed and synthesized as anticonvulsant drugs. Acyclic derivative consist of phosphinic, (thio)phos-phonic, phosphoric and phosphorous acids and esters possessing an amino group gamma to a phosphoryl moiety. These are structually related to gamma-aminobutyric acid (GABA) and are expected to serve as GABA-mimetics of GABA-transaminase reversible or irreversible inhibitors. The cyclic compounds are 1,2,-aza-phospholidines, 1,3,4,-diaza or 1,3-azaphospholidines and 1,3,2-oxazaphospholidines which are analogues of succinimide, hydantoin and oxazolidinediones, respectively. All new agents will have their log P (octanol-water) values experimentally determined using high pressure liquid chromatography. These potential anticonvulsants have calculated log P values of plus 1.41 to plus 3.33, a range encompassing the log P value of plus 2 previously established as optimum for agents capable of gaining access to the central nervous system. The new agents will be submitted to NINCDS for pharmacological evaluation and this data, with the experimentally determined log P values, will be subjected to a computer-based multiple regression analysis to guides and optimize the design and synthesis of subsequent drugs.